Method of synthesis of methoxyheptyl bicyclooctanone

Abstract

Described is a method of synthesizing 6-(5-ethoxyhept-1-yl)bicyclo[3.3.0] octan-3-one by reacting 3-(5-ethoxyhept-1-yl) cyclopentene with dichloroketene. The resulting reaction products are reacted with acetic acid and zinc to produce 4-(5-ethoxyhept-1-yl)bicyclo[3.2.0]heptan-6-one and 4-(5-ethoxyhept-1-yl)bicyclo [3.2.0]heptan-7-one, which are reacted with trimethylsulfonium iodide to produce 2-(5-ethoxyhept-1-yl)spiro[bicyclo[3.2.0]heptane-6,2′-oxirane] and 4-(5-ethoxyhept-1-yl)spiro-[bicyclo-[3.2.0]heptane-6,2′-oxirane]. Lithium iodide is reacted with 2-(5-ethoxyhept-1-yl)spiro[bicyclo[3.2.0]heptane-6,2′-oxirane] and 4-(5-ethoxyhept-1-yl)spiro-[bicyclo-[ 3.2.0]heptane-6,2′-oxirane] to produce 6-(5-ethoxyhept-1-yl)bicyclo[3.3.0]octan-3-one. A method of synthesizing 6-(5-methoxyhept-1-yl)bicyclo[3.3.0]octan-3-one is also described.

The invention claimed is: 
     
       1. A method of synthesizing a compound, the method comprising:
 reacting a first mixture comprising 
 7,7-dichloro-4-(5-methoxyhept-1-yl)bicyclo[3.2.0]heptan-6-one and 6,6-dichloro-4-(5-methoxyhept-1-yl)bicyclo[3.2.0]heptan-7-one with acetic acid and zinc to form a second mixture comprising 4-(5-methoxyhept-1-yl)bicyclo[3.2.0]heptan-6-one and 4-(5-methoxyhept-1-yl) bicyclo[3.2.0]heptan-7-one; 
 reacting the second mixture with trimethylsulfonium iodide to form a third mixture comprising 2-(5-methoxyhept-1-yl)spiro[bicyclo[3.2.0]heptane-6,2′-oxirane] and 4-(5-methoxyhept-1-yl)-spiro[bicyclo[3.2.0]heptane-6,2′-oxirane]; and reacting the third mixture with a Lewis acid to form 6-(5-methoxyhept-1-yl)bicyclo[3.3.0] octan-3-one. 
 
     
     
       2. The method according to  claim 1 , wherein reacting a first mixture with acetic acid and zinc to form a second mixture comprises reacting the first mixture with acetic acid and zinc without distilling the first mixture. 
     
     
       3. The method according to  claim 1 , wherein reacting the second mixture with trimethylsulfonium iodide to form a third mixture comprises adding trimethylsulfonium iodide, sodium hydride, and dimethylsulfoxide to the second mixture. 
     
     
       4. The method according to  claim 1 , wherein reacting the third mixture with a Lewis acid to form 6-(5-methoxyhept-1-yl)bicyclo[3.3.0]octan-3-one comprises dissolving the 2-(5-methoxyhept-1-yl)spiro[bicyclo[3.2.0]heptane-6,2′-oxirane] and 4-(5-methoxyhept-1-yl)spiro[bicyclo[3.2.0]heptane-6,2′-oxirane] in tetrahydrofuran and adding a solution of lithium iodide in tetrahydrofuran. 
     
     
       5. The method according to  claim 1 , wherein reacting the third mixture with a Lewis acid to form 6-(5-methoxyhept-1-yl)bicyclo[3.3.0]octan-3-one comprises filtering and concentrating the 6-(5-methoxyhept-1-yl)bicyclo[3.3.0] octan-3-one. 
     
     
       6. The method according to  claim 1 , further comprising purifying the 6-(5-methoxyhept-1-yl)bicyclo[3.3.0]octan-3-one. 
     
     
       7. The method according to  claim 1 , wherein reacting the third mixture with a Lewis acid comprises reacting the third mixture with lithium iodide. 
     
     
       8. The method according to  claim 1 , wherein reacting a first mixture with acetic acid and zinc comprises reacting zinc with the 7,7-dichloro-4-(5-methoxyhept-1-yl)bicyclo[3.2.0]heptan-6-one and 6,6-dichloro-4-(5-methoxyhept-1-yl)bicyclo[3.2.0]heptan-7-one in a solution of acetic acid. 
     
     
       9. The method according to  claim 1 , wherein reacting the second mixture with trimethylsulfonium iodide comprises reacting the second mixture with trimethylsulfonium iodide and sodium hydride.